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The immune system of the female genital tract: The effects of human immunodeficiency virus infection

Olaitan, Adeola; (1998) The immune system of the female genital tract: The effects of human immunodeficiency virus infection. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

This project was designed to investigate the immune function of the healthy female cervix and to determine how this may be affected in human immunodeficiency virus (HIV) disease. Immunohistochemical, in situ hybridisation and polymerase chain reaction techniques were applied to determine the distribution of immunocompetent cells, the cytokine profile and HIV load in cervical biopsies obtained at colposcopy from 40 HIV-positive and 20 HIV-negative women. The findings were correlated with peripheral immune status, as determined by peripheral CD4 lymphocyte count and HIV load. Cervical biopsy sections from HIV-positive women showed significantly decreased Langerhans' cell counts in the epithelium and significantly increased T lymphocytes in the sub-epithelial stroma compared with HIV-negative women. There was an increase in CD8+ lymphocytes in sections from HIV-positive women, leading to an inversion of the CD4/CD8 ratio compared with HIV-negative women. The majority of these CD8+ cells were 'primed' (CD45ro+) but they showed a reduced expression of cytolytic granules (perforin negative, low TIA-1) and impaired survival ability (Bcl-2 low). These changes occurred in advance of systemic immunosuppression. The cervical biopsy sections from HIV-infected women had decreased mRNA for the Th-1 cytokine, Interleukin-2 (IL-2) and increased IL-4, IL-5, IL-10 mRNA (Th-2 cytokines) compared with HIV-negative women, but there was no significant difference in Interferon-y mRNA. Viral load studies showed a higher HIV in cervical tissue than in serum. There was no correlation between HIV disease stage and cervical cytokine mRNA or viral load. These observations suggest that HIV-infected women mount an impaired cytotoxic lymphocyte response at a local level which may affect their ability to resist genital tract infections and cervical neoplastic change. Increased production of inhibitory cytokines (IL-4 and IL-10) may, in part, account for the chronicity of the virus in cervical tissues. High viral load in cervical tissues may contribute to the high risk of vertical transmission in the peripartum period.

Type: Thesis (Doctoral)
Qualification: M.D
Title: The immune system of the female genital tract: The effects of human immunodeficiency virus infection
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10103793
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